The dialysis population is growing rapidly, with more than 100,000 patients starting treatment every year. The great majority of these patients receive hemodialysis three times per week from the onset of therapy despite most having substantial residual function. While thrice weekly treatment remains standard, recent years have seen renewed interest in reducing treatment frequency for patients with residual native kidney function. It seems logical that if patients retain some kidney function, they do not need as much hemodialysis. Current guidelines indeed allow reduction in dialysis frequency to twice weekly based on residual function. However, fewer than 2% of patients receive hemodialysis twice weekly. There are two major reasons why twice weekly hemodialysis is prescribed so rarely. First, no controlled study has ever assessed the effect of prescribing twice weekly treatment using the current guidelines. The second impediment is the misconception that very long treatment times are required for twice weekly treatment. It is not widely appreciated that current 2015 guidelines reduced the dialysis dose for patients with residual kidney function so that treatment times for twice weekly hemodialysis are no longer dramatically high. The proposed study will be the first to compare the efficacy of twice weekly and thrice weekly hemodialysis in patients with residual function. It will employ a cross-over design consisting of two 4-week periods. During one period, treatment will be provided twice weekly with residual kidney function incorporated into the prescription as specified by the current guidelines. During the other period, treatment will be provided thrice weekly regardless of the residual kidney function as is the current common practice. The first aim is to assess the effect of twice weekly hemodialysis on quality of life. We will test the hypothesis that quality of life is not impaired by a change from the current practice of prescribing thrice weekly dialysis without regard to residual function to prescribing twice weekly dialysis incorporating residual kidney function as specified by the guidelines. The second aim is to assess the effect of twice weekly hemodialysis on plasma levels of uremic solutes, which are normally cleared by secretion. It will test the hypothesis that levels of these secreted solutes are only minimally increased by a change from the current practice of prescribing thrice weekly dialysis without regard to residual function to prescribing twice weekly dialysis incorporating residual function. The 2015 guidelines acknowledged that the remnant kidney performs valuable functions which are not reflected by the removal of urea, the current marker solute. One such function is solute secretion, which is preserved in the remnant kidney and not replicated by hemodialysis. Positive results from the proposed study would encourage increased prescription of twice weekly hemodialysis when sufficient residual function is present. This shift would reduce the burden and cost of treatment. Overall results of the proposed study would provide a foundation for future trials of twice weekly hemodialysis.